3-(Methylthio)-1-propanol → 4-(4-Bromo-2-fluoroanilino)-6-methoxy-7-(3-methylthiopropoxy)quinazoline

HRID 1838561

반응식

HRID 1838561 반응식
N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.[CH3:19][S:20][CH2:21][CH2:22][CH2:23][OH:24].[Br:25][C:26]1[CH:45]=[CH:44][C:29]([NH:30][C:31]2[C:40]3[C:35](=[CH:36][C:37](O)=[C:38]([O:41][CH3:42])[CH:39]=3)[N:34]=[CH:33][N:32]=2)=[C:28]([F:46])[CH:27]=1.C(P(CCCC)CCCC)CCC>C(Cl)Cl>[Br:25][C:26]1[CH:45]=[CH:44][C:29]([NH:30][C:31]2[C:40]3[C:35](=[CH:36][C:37]([O:24][CH2:23][CH2:22][CH2:21][S:20][CH3:19])=[C:38]([O:41][CH3:42])[CH:39]=3)[N:34]=[CH:33][N:32]=2)=[C:28]([F:46])[CH:27]=1

참가 물질

6

반응물 4

HCID 104483-(Methylthio)-1-propanolHCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 1355038524-[(4-Bromo-2-fluorophenyl)amino]-6-methoxy-7-quinazolinol

생성물 1

HCID 224782814-(4-Bromo-2-fluoroanilino)-6-methoxy-7-(3-methylthiopropoxy)quinazoline수율 50%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

반응 조건

온도
5 °C

실험 절차

1,1′-(Azodicarbonyl)dipiperidine (1.56 g, 6.2 mmol) followed by 3-(methylthio)-1-propanol (0.32 ml, 3 mmol) was added to a mixture of 4-(4-bromo-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (225 mg, 7.0 mmol), (prepared as described for the starting material in Example 48), and tributylphosphine (1.42 ml, 6.1 mmol) in methylene chloride (20 ml) at 5° C. The mixture was stirred at 5° C. for 1 hour and then for 18 hours at ambient temperature. The insolubles were removed by filtration and the volatiles were removed from the filtrate by evaporation. The residue was purified by column chromatography eluting with ethyl acetate/methanol (100/0 increasing to 95/5) to give 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-(3-methylthiopropoxy)quinazoline (400 mg, 50%).

후처리

  1. custom(prepared
  2. customat 5° C
  3. waitfor 18 hours at ambient temperature
  4. customThe insolubles were removed by filtration
  5. customthe volatiles were removed from the filtrate by evaporation
  6. customThe residue was purified by column chromatography
  7. washeluting with ethyl acetate/methanol (100/0 increasing to 95/5)

출처 및 근거

ORD 기록
ord-41a55bc195194d4e880b8682f146e898
출처 데이터셋
uspto-grants-2004_01
특허 번호
US06673803B2

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